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EP1656954B2 - Solutions d'albumine humaine thérapeutiques ayant une faible activité de l'activateur de la prékallikréine (PKA) et procédés de production - Google Patents
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EP1656954B2 - Solutions d'albumine humaine thérapeutiques ayant une faible activité de l'activateur de la prékallikréine (PKA) et procédés de production - Google Patents

Solutions d'albumine humaine thérapeutiques ayant une faible activité de l'activateur de la prékallikréine (PKA) et procédés de production Download PDF

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Publication number
EP1656954B2
EP1656954B2 EP05380116.3A EP05380116A EP1656954B2 EP 1656954 B2 EP1656954 B2 EP 1656954B2 EP 05380116 A EP05380116 A EP 05380116A EP 1656954 B2 EP1656954 B2 EP 1656954B2
Authority
EP
European Patent Office
Prior art keywords
antithrombin
albumin
obtaining
pka
extraction
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
EP05380116.3A
Other languages
German (de)
English (en)
Other versions
EP1656954B1 (fr
EP1656954A1 (fr
Inventor
Juan Ignacio Jorquera Nieto
Olga Santaeularia Lozano
Nuria Hosta Mateu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Grifols SA
Original Assignee
Grifols SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=34072931&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=EP1656954(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Grifols SA filed Critical Grifols SA
Priority to DE602005003426.9T priority Critical patent/DE602005003426T3/de
Priority to PL05380116T priority patent/PL1656954T4/pl
Publication of EP1656954A1 publication Critical patent/EP1656954A1/fr
Publication of EP1656954B1 publication Critical patent/EP1656954B1/fr
Application granted granted Critical
Publication of EP1656954B2 publication Critical patent/EP1656954B2/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • A61K51/081—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins the protein being an albumin, e.g. human serum albumin [HSA], bovine serum albumin [BSA], ovalbumin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock

Definitions

  • the present disclosure relates generally to therapeutic human albumin solutions with low prekallicrein activator (PKA) activity, which are stable over time.
  • PKA prekallicrein activator
  • the present invention relates to a process for reducing prekallicrein activator activity in purified albumin solutions of human origin.
  • the subject matter of the invention is as set out in the appended claims.
  • Coagulation factor XII (Hageman factor) is a protein having a molecular weight of approximately 80,000 which, in its activated form, consists of fragments thereof having a molecular weight of approximately 28,000. This activated factor XII (fXIIa) acts as a prekallicrein activator (PKA).
  • PKA prekallicrein activator
  • PKA acts on prekallicrein, catalysing its conversion to kallicrein which adversely affects the conversion from kininogen to bradykinin.
  • Bradykinin is a potent vasodilator which can cause incidences of hypotension.
  • the kallicrein formed also catalyses the formation of PKA, feeding back the process.
  • Purified human plasma albumin solutions are therapeutically useful and are widely used to increase blood volume in cardiovascular surgery, among other uses.
  • PKA may be present as a contaminant in these human albumin solutions, as it is generated from factor XII by contact with foreign surfaces during the albumin purification process and for other reasons, so its content in said solutions has been limited to levels of less than 35 IU/ml (European Pharmacopoeia).
  • the inventors proposed to find therapeutic human albumin solutions having low prekallicrein activator (PKA) activity and also ensuring significant stability of the PKA levels in the commercial albumin solution for the established storage period so that a therapeutic human albumin solution with a very low level of prekallicrein activator is clinically available at any time within a previously established long storage period.
  • PKA prekallicrein activator
  • the disclosed albumin solution is obtained by partial extraction of the antithrombin in a phase of fractionation of human plasma, and, in particular, by chromatographic extraction, for example, from the plasma, the cryoprecipitation supernatant, the fraction I supernatant or the II+III supernatant.
  • This partial extraction of the antithrombin may be carried out by influencing the parameters that control the chromatographic stage, for example by varying the chromatography load relationship, so that the effluent contains sufficient antithrombin to detect a concentration greater than or equal to 0.03 mg of active antithrombin/g of albumin in the final albumin.
  • only a portion of the total volume that will yield the final batch of albumin is subjected to chromatographic extraction, the materials that have been subjected to extraction subsequently being mixed with those that have not been extracted.
  • This may be achieved by mixing plasmas, supernatants (of cryoprecipitate, FrI or FrII+III) or fractions (FrIV or FrV) from which the antithrombin has been extracted with others that have not been subjected to said extraction.
  • This mixture should be in a proportion that is sufficient to detect an antithrombin concentration greater than or equal to 0.03 mg of antithrombin/g of albumin in the final albumin.
  • Example 1 albumin was prepared from FrV, and the antithrombin was extracted from the FrII+III supernatant by heparin-agarose affinity chromatography.
  • Table 1 shows the antithrombin content of the albumin (final product in concentration of 20%) as a function of the percentage (%) of the volume of FrII+III supernatant from which the antithrombin has been extracted by chromatography.
  • the antithrombin was extracted in supernatant fractions of 0, 50, 80 and 100% respectively while mixing with the corresponding portions of FII+FIII without antithrombin extraction.
  • Table 2 shows the development over time at 5° C of PKA activity (UI) in 20 % albumin solutions (fmal product) in relation to the percentage of extraction of antithrombin achieved in the FrII+III supernatant.
  • Table 2 process Extraction of anti-thrombin (%) Months 0 1 2 3 5 6 8 9 12 1 0 ⁇ 2.0 ⁇ 2.0 ⁇ 2.0 -- 2.4 -- ⁇ 2.0 -- ⁇ 2.0 2 0 ⁇ 2.0 ⁇ 2.0 ⁇ 2.0 -- ⁇ 2.0 -- ⁇ 2.0 3 50 ⁇ 2.0 ⁇ 2.0 ⁇ 2.0 -- ⁇ 2.0 -- ⁇ 2.0 -- ⁇ 2.0 4 50 ⁇ 2.0 ⁇ 2.0 ⁇ 2.0 -- ⁇ 2.0 -- 2.5 5 80 ⁇ 2.0 ⁇ 2.0 -- 2.9 3.0 -- -- 3.2 5.7 6 80 2.2 3.0 3.5 4.4 -- 2.3 -- 6.0 5.6 7 100 8.9 18.5 -- 18.2 15.4 -- -- 22.3 24.2 8 100 10.6 23.3 -- 24.9 24.0 -- -- 32.1 32.8

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)

Claims (8)

  1. Procédé pour réduire l'activité de l'activateur de prékallicréine (PKA) dans des solutions d'albumine purifiée d'origine humaine et pour leur stabilisation dans le temps, caractérisé par l'extraction partielle de l'antithrombine pendant le fractionnement du plasma humain de sorte que l'albumine finale a une teneur en antithrombine active égale ou supérieure à 0,03 mg/g d'albumine.
  2. Procédé selon la revendication 1 caractérisé en ce que l'extraction partielle contrôlée de l'antithrombine est réalisée par chromatographie.
  3. Procédé pour obtenir de l'albumine selon la revendication 1 caractérisé en cc que l'extraction chromatographique de l'antithrombine est réalisée dans le plasma.
  4. Procédé pour obtenir de l'albumine selon la revendication 1 caractérisé en ce que l'extraction chromatographique de l' antithrombine est réalisée dans le surnageant de cryoprécipitation.
  5. Procédé pour obtenir de l'albumine selon la revendication 1 caractérisé en ce que l'extraction chromatographique de l'antithrombine est réalisée dans le surnageant de la fraction I.
  6. Procédé pour obtenir de l'albumine selon la revendication 1 caractérisé en ce que l'extraction chromatographique de l'antithrombine est réalisée dans le surnageant de la fraction II+III.
  7. Procédé pour obtenir de l' albumine selon la revendication 1 caractérisé en ce que l'antithrombine est extraite par chromatographie d'affinité.
  8. Procédé pour obtenir de l'albumine selon la revendication 1 caractérisé en cc que l'antithrombine est extraite par chromatographie d'échange d'ions.
EP05380116.3A 2004-07-26 2005-06-03 Solutions d'albumine humaine thérapeutiques ayant une faible activité de l'activateur de la prékallikréine (PKA) et procédés de production Expired - Lifetime EP1656954B2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
DE602005003426.9T DE602005003426T3 (de) 2004-07-26 2005-06-03 Therapeutische Humanalbuminlösungen mit niedriger Präkallikreinaktivator- (PKA)-Aktivität und Verfahren zu deren Herstellung
PL05380116T PL1656954T4 (pl) 2004-07-26 2005-06-03 Terapeutyczne roztwory ludzkiej albuminy z niską aktywnością aktywatora prekalikreiny i sposób ich otrzymywania

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
ES200401830A ES2221817B1 (es) 2004-07-26 2004-07-26 "soluciones de albumina humana terapeutica con baja actividad del activador de precalicreina (pka) y procedimiento de obtencion de las mismas".

Publications (3)

Publication Number Publication Date
EP1656954A1 EP1656954A1 (fr) 2006-05-17
EP1656954B1 EP1656954B1 (fr) 2007-11-21
EP1656954B2 true EP1656954B2 (fr) 2021-04-28

Family

ID=34072931

Family Applications (1)

Application Number Title Priority Date Filing Date
EP05380116.3A Expired - Lifetime EP1656954B2 (fr) 2004-07-26 2005-06-03 Solutions d'albumine humaine thérapeutiques ayant une faible activité de l'activateur de la prékallikréine (PKA) et procédés de production

Country Status (10)

Country Link
US (2) US7332577B2 (fr)
EP (1) EP1656954B2 (fr)
JP (1) JP4584788B2 (fr)
AU (1) AU2005202654B2 (fr)
BR (1) BRPI0502744B8 (fr)
DE (1) DE602005003426T3 (fr)
ES (2) ES2221817B1 (fr)
MX (1) MXPA05005915A (fr)
PL (1) PL1656954T4 (fr)
PT (1) PT1656954E (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101702334B1 (ko) * 2015-04-28 2017-02-06 동양피스톤 주식회사 피스톤용 냉각 튜브, 링 캐리어 어셈블리, 피스톤 및 이를 이용한 피스톤 제조 방법
US12161777B2 (en) 2020-07-02 2024-12-10 Davol Inc. Flowable hemostatic suspension
US11739166B2 (en) 2020-07-02 2023-08-29 Davol Inc. Reactive polysaccharide-based hemostatic agent
JP2024500994A (ja) 2020-12-28 2024-01-10 デボル，インコーポレイテッド タンパク質及び多官能化変性ポリエチレングリコール系架橋剤を含む反応性乾燥粉末状止血用材料

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS597693B2 (ja) * 1978-01-07 1984-02-20 株式会社ミドリ十字 抗トロンビン製剤及びその製法
US4378346A (en) * 1979-08-15 1983-03-29 Tankersley Donald L Intravenously injectable solution of plasma protein fraction free from bradykinin, kininogen and prekallikrein activators and processes for its production
US4251510A (en) * 1979-08-15 1981-02-17 Cutter Laboratories, Inc. Intravenously injectable solution of plasma protein fraction free from bradykinin, kininogen and prekallikrein activators and processes for its production
DE3612137A1 (de) * 1986-04-10 1987-10-15 Biotest Pharma Gmbh Steriles plasmaaustauschmittel
DE3622642A1 (de) * 1986-07-05 1988-01-14 Behringwerke Ag Einkomponenten-gewebekleber sowie verfahren zu seiner herstellung
FR2610633B1 (fr) * 1987-02-05 1992-09-18 Lille Transfusion Sanguine Procede d'obtention d'un concentre d'a 1-antitrypsine a partir de plasma humain et son utilisation a titre de medicament
AT391810B (de) * 1988-02-26 1990-12-10 Immuno Ag Verwendung von chymotrypsin zum unwirksammachen des praekallikrein-aktivators
FR2648048B1 (fr) * 1989-06-08 1994-06-03 Lille Transfusion Sanguine Procede de preparation de solutions d'albumine purifiee
ES2103236B1 (es) * 1996-01-30 1998-04-16 Grifols Grupo Sa Albumina humana terapeutica con baja capacidad para la fijacion de aluminio.
AU4837996A (en) * 1996-02-29 1997-09-16 Delta Biotechnology Limited High purity albumin production process
WO2000056768A2 (fr) * 1999-03-19 2000-09-28 Bayer Corporation Procede de preparation d'albumine par chromatographie
BR0316563A (pt) * 2002-11-25 2005-10-04 Octapharma Ag Fração de albumina derivada de plasma exaurido de prekallikrein

Also Published As

Publication number Publication date
PT1656954E (pt) 2008-02-14
EP1656954B1 (fr) 2007-11-21
ES2294664T5 (es) 2021-11-30
US8084580B2 (en) 2011-12-27
AU2005202654B2 (en) 2007-04-05
US20070161781A1 (en) 2007-07-12
PL1656954T3 (pl) 2008-04-30
JP4584788B2 (ja) 2010-11-24
DE602005003426D1 (de) 2008-01-03
DE602005003426T3 (de) 2021-09-02
JP2006036771A (ja) 2006-02-09
DE602005003426T2 (de) 2008-10-02
ES2221817B1 (es) 2005-10-01
PL1656954T4 (pl) 2008-08-29
US7332577B2 (en) 2008-02-19
ES2221817A1 (es) 2005-01-01
BRPI0502744B1 (pt) 2019-02-26
BRPI0502744A (pt) 2006-05-02
US20060020117A1 (en) 2006-01-26
EP1656954A1 (fr) 2006-05-17
BRPI0502744B8 (pt) 2021-05-25
ES2294664T3 (es) 2008-04-01
AU2005202654A1 (en) 2006-02-09
MXPA05005915A (es) 2006-01-30

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